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| United States Patent |
6,180,106
|
|
Keller
, et al.
|
January 30, 2001
|
Symptomatic relief of allergic reactions
Abstract
The composition disclosed is a unique formulation of Traditional Chinese
Medicine (TCM) extracts created to reduce the debilitating symptoms of
allergies. It combines a number of organically grown, but, non-organically
extracted, standardized formulations of natural ingredients which have
been used singly for hundreds of years for symptomatic relief of
allergies. These include Ginseng and Gan Cao, which provide a natural
anti-inflammatory effect; Bai Gao, which prevent the smooth muscle spasms
associated with allergic reactions; Suan Zao ren, which provides an
antihistamine effect without the usual sedative effect; and Wu Mai, which
reduces the local swelling associated with allergies. Combined, it was
unexpectedly found that these ingredients provide a natural, non-drying,
non-sedating alternative to antihistamines, without inhibiting the natural
healing mechanisms.
| Inventors:
|
Keller; Robert H (Weston, FL);
Wen; Xue-Lan (Miami, FL)
|
| Assignee:
|
Vit-Immune, L.C. (Hollywood, FL)
|
| Appl. No.:
|
349100 |
| Filed:
|
July 8, 1999 |
| Current U.S. Class: |
424/757 |
| Intern'l Class: |
A01N 065/00; A61K 035/78 |
| Field of Search: |
424/195.1
514/783
|
References Cited
U.S. Patent Documents
| 5584140 | Dec., 1996 | Byrne | 47/58.
|
| 5874084 | Feb., 1999 | Yng-Wong | 424/195.
|
Other References
Computer JPAB Abstract Yutaka et al JP407048267 Crude-Drug Extract
Containing Ginkgo-Leaf Extract and Prunus Mume Immature Fruit Extract And
Health Drink Containing The Crude-Drug Extract Feb. 21, 1995.
Computer JPAB Abstract JP 62096428 Refreshing Drink Containing Plum
Component, May 1987.
Computer Derwent Abstract Gong et al CN 1196954 Compound Gingko Leaf
Preparation And Its Prep Method Oct. 28, 1998, Feb. 1995.
|
Primary Examiner: Lilling; Herbert J.
Attorney, Agent or Firm: Pitney, Hardin, Kipp & Szuch, LLP
Parent Case Text
This application claims priority to U.S. Provisonal Application Ser. No.
60/092,352 filed Jul. 10, 1998.
Claims
What is claimed is:
1. A composition of matter, comprising an admixture of particles of the
following ingredients:
gingseng root;
gingko biloba leaf;
Ziziphus seed;
mume fruit;
licorice root;
wherein the composition comprises at least about 3% of each of said
ingredients.
2. The composition of claim 1 where the composition comprises at least 10%
of each of the following ingredients: mume fruit and licorice root.
3. The composition of claim 1 further comprising flavorants.
4. The composition of claim 1 further comprising a liquid or solid
pharmaceutically acceptable carrier.
5. The systemic administration of a pharmaceutically effective amount of
the composition according to claim 1 or 2 to a mammal suffering a type I
hypersensitivity reaction to an allergen, for the relief of symptoms
associate with the reaction.
6. The systemic administration of a pharmaceutically effective amount of
the composition according to claim 1 to a mammal suffering a type I
hypersensitivity reaction to an allergen, for the relief of symptoms
associate with the reaction.
7. The systemic administration of a pharmaceutically effective amount of
the composition according to claim 2 to a mammal suffering a type I
hypersensitivity reaction to an allergen, for the relief of symptoms
associate with the reaction.
8. The systemic administration of a pharmaceutically effective amount of
the composition according to claim 1 to a mammal to act as a cough
suppressant.
9. The systemic administration of a pharmaceutically effective amount of
the composition according to claim 1 to a mammal to suppress itching.
10. The topical administration of a pharmaceutically effective amount of
the composition with a pharmaceutically acceptable carrier according to
claim 1 to a mammal to suppress itching.
11. The systemic administration of a pharmaceutically effective amount of
the composition according to claim 1 to a mammal to act as an
antihistamine.
12. The systemic administration of a pharmaceutically effective amount of
the composition according to claim 1 to a mammal to act as an
anti-inflammatory.
13. The systemic administration of a composition according to claim 1 of a
dosage of 0.1 mg/kg to about 50 mg/kg of body weight of the mammal, daily.
14. The systemic administration of a composition according to claim 1 of a
dosage of 0.5 mg/kg to about 25 mg/kg of body weight of the mammal, daily.
Description
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to pharmaceutical compositions and methods for the
treatment of mammals suffering symptoms of allergic reactions.
2. Brief Description of Related Art
An allergy is defined as an immune response in a mammal induced by an
environmental antigen that has deleterious effects resulting in
significant tissue damage and inflammation. Allergies comprise one of the
most common medical problems in the twentieth century with some estimates
suggesting that as many at 10% of the population may be affected. The
antigen (allergen) is a non-parasitic antigen and the immune response is
generally a type I hypersensitivity reaction. This reaction, which
comprises mast cell or basophil degranulation manifests itself clinically
in disorders related to biological effects of mediators released by the
degranulation. These mediators are pharmacologically active agents that
act on local tissues to increase vascular permeability and inflammation.
Primary mediators such as histamine, serotonin, protease, prostaglandins
SRS-A and similar substances released during degranulation may actually be
more detrimental than beneficial to the comfort and well-being of the
affected individual. The biological effects are the symptoms of the
hypersensitivity reactions.
The classical treatment of type I hypersensitivity reactions has heretofore
comprised administration of, for example, antihistamines or a process
termed desensitization. Desensitization involves multiple injections and
requires frequent visits to a doctor over a long period of time.
Antihistamines are, of course, effective to relieve the symptoms
associated with the type I hypersensitivity reaction. Antihistamine
treatment suffers from problems including drying of the mucous membranes
and sedation as well as manifest side effects of depression and
drowsiness. In addition, antihistamines can interact with other medicines.
Warnings are given to refrain from operating machinery when antihistamines
are administered. Both methods are expensive.
Ideally, the treatment of the symptoms associated with allergic
hypersensitivity reactions avoids the administration of antihistamines or
blocks the other mediators in the allergic cascade causing a reduction in
the symptoms.
It has been observed that traditional Chinese pharmacopoeia includes
medicinals which have been time-tested for safety and effectiveness. For
example, ginseng has been used in China for over 5,000 years. In a
traditional Chinese medical context, ginseng is a "tonic" or "adaptogen"
considered by many to be a substance which is not harmful and causes
minimal changes or symptoms in the physiological functions of an organism.
This herbal root is used throughout Asia to promote an overall sense of
well being, stamina and strength. In this regard, it is believed by many
that ginseng preparations act to modulate stress, replenish vital energy,
improve performances under a wide variety of stressful conditions,
increase blood volume, promote appetite, quiet the spirit and provide
wisdom. It is, in fact, listed in the Merck Index as therapeutically an
"aromatic bitter".
However, even in traditional Chinese medicine ginseng is not considered a
panacea. The general practioner, after determining a diagnosis and before
prescribing medication, will map a course of treatment strategy. When he
prescribes medication, including ginseng, he will always prescribe the
ginseng in combination with some other remedy which, depending on the
diagnosis, will operate in the same direction or in the opposite direction
to bring the yin and yang into balance, even though the condition under
treatment may respond to administration of ginseng alone.
SUMMARY OF THE INVENTION
The invention comprises a composition for oral or local administration to a
mammal suffering a type I hypersensitivity reaction to an allergen, for
the relief of symptoms associated with the reaction, which comprises; in
admixture, particlized
ginseng root;
Ginko biloba leaf;
Ziziphus seed;
mume fruit; and
licorice root.
The invention also comprises a method for the symptomatic relief of a type
I hypersensitivity reaction in a mammal, which comprises orally
administering to said mammal an effective dose for said relief, of a
mixture of ginseng root, Ginko biloba leaf, Ziziphus seed, mume fruit and
licorice root.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS OF THE INVENTION
Those skilled in the art will gain an appreciation of the invention from
the following discussion of the preferred embodiments of the invention.
Ginseng (called "renshen" in Chinese) is the root of a botanical, found
naturally in China and Korea. The best known ginseng on a worldwide basis
is Asian ginseng (Panax ginseng), which is also widely cultivated in the
United States. There are other varieties, such as Siberian ginseng
(Eleutheroccus senticosus). The root comprises resin, panaxatriol and
other substances containing a steroid nucleus, sugar, starch, mucilage, a
saponin, volatile oil or triterpenoid glycosides including, in particular,
P. quinquefolium and P. pseudoginseng which are generally considered to be
biologically active. Isolation and identification of ginseng saponins is
described in Kaku et al., Arzneimittel-Forsch. 25, 343 (1975). Use in
oriental medicine as tonic: K. Chimin Wong, Wu Lien-the, History of
Chinese Medicine (Shanghai, 2nd ed., 1936) 906 pp. Comprehensive review of
morphology, cultivation and uses appears in Baranov, Econ. Bot. 20,
403-406 (1966).
As a therapeutic composition, Ginseng is classified as an aromatic bitter;
Merck Index, No. 4256. It has a sweet, aromatic taste which can be
referred to as "exotic".
Research suggests to some that ginseng has nonspecific immunostimulatory
activity similar to that of the herb Echinacea.
The present invention does not make any claim for curative benefit from the
use of ginseng, but suggests that its inclusion in the composition of the
invention has accepted advantages, including but not limited to at least
some of the advantages mentioned above.
Dried ginseng root is generally administered to adults in doses of 2 to 8
grams per day (when used singly).
The leaf of the Ginkgo biloba tree is rich in flavonoid glycosides content
along with ginkogolides and bilbalides. Ginkgo biloba is a chemical
mediator of allergic symptoms in the group of substances termed
leukotrienes. Although these chemicals are partially inhibited by
licorice, they are more completely inhibited by Ginkgo. As such, these
herbs in combination serve to more effectively block the inflammatory
component of allergies by inhibiting the effects of multiple inflammatory
mediators. Extracts of the leaf (24% extract) are commercially available
from a number of providers (for example, Boehringer Ingelheim
Pharmaceuticals, Inc., Ridgefield, Conn.) who manufacture a standardized
24 percent extract. The extract (Chinese name: bai goo) has been
identified as a mild sedative which prevents smooth muscle spasms
associated with type I hypersensitivity reactions. The herb is also a
stimulant to the circulatory system. The dosage administered to adults is
generally within the range of 40 to 120 mg/per day (when used singly).
The seed of Ziziphus jujuba (Rhamnaceae) known in China as suan zao ren
provides an antihistamine effect without the usual sedative side effect.
This herb acts as a general calmer to the immune system without
compromising its ability to defend us from bacteria, viruses etc. Suan zao
ren functions in allergic reactions to decrease the levels of symptoms by
decreasing immune chemicals. In addition, it contains Vitamin C which also
has been shown to be protective in allergic conditions. It may be
administered to adults in a dosage of from 6 to 15 gms/day (used singly).
The Chinese use this medication to calm the nerves and relax the body.
Commonly called licorice root, the root of Glycyrrhiza uralensis
(leguminosae) known also as "gan cao" or Chinese licorice is used in
Chinese medicine to slow and prolong the effect of strong tonics. In
combination with the ginseng it functions to provide a prolonged
anti-inflammatory effect. It is generally administered to adults in a
dosage of 2 to 10 grams/day (when used singly). Equivalent sources of
glycyrrhiza are the root of G. glabra L. variety typica (Spanish licorice)
and other varieties containing 6-14 percent of glycyrrhizn (the glucoside
of glycyrrhetic acid). Inflammation is a central phenomenon associated
with all allergic reactions and the reason that allergic symptoms are
frequently treated with local steroids as well as antihistamines. Licorice
provides a natural alternative and in conjunction with Ginseng provides
both a significant anti-inflammatory as well as an antihistamine effect.
In addition, it provides a natural suppressant for the coughs that
commonly accompany allergic reactions.
The unripened, dried fruit of the tree Prunus mume known as "black-plums"
and known in China wu mei, is possessive of astringent properties. This
traditional Chinese herb has a variety of effects. In the context of
allergies, however, it has both a direct antihistaminic effect as well as
preventing the vascular leakiness associated with sever allergies. The
mechanism by which this occurs remains obscure. When used in the present
invention at a dosage of 100 to 600 mg per day, the ingredient functions
to reduce local swelling, of tissues, associated with the type I
hypersensitivity reaction.
The ingredients described above in combination, work synergistically to
provide the necessary action required for response to type I
hypersensitivity reaction to an allergen, while supporting the mammal's
ability to heal itself since administration of the combination does not
inhibit natural tissue repair mechanisms. The ingredients work together to
calm the biochemical triggers and clinical symptoms of allergies without
the expense and inconvenience of desensitization or the sedating and
drying effects of antihistamines. This gains importance as allergic
symptoms (which result from the release of chemicals from the surface of
basophils and mast cells) are caused not only by histamine but by a
variety of chemicals. As a result, antihistamines, the most commonly used
anti-allergy therapy, cannot totally block symptoms as they do not prevent
the actions of other released chemicals.
As each of these ingredients has properties which enhances the properties
of the others, it is preferable that there be at least 3% of each of the
ingredients in the compound. In more preferred embodiments, there is at
least 10% of each of the following ingredients: Ziziphus seed; mume fruit;
and licorice root. It will be appreciated that the proportion of the
ingredients may be adjusted to address the individual needs of patients
depending on the severity of the various symptoms of allergies such as
sneezing, coughing, stuffy nose, headaches, nausea, itching, and various
other associated symptoms.
Clinical Testing
The efficacy of the compound has been demonstrated in clinical tests. Ten
patients were on a treatment of prescription antihistamines (sold under
the trademarks Claritin.RTM. or Zyrtec.RTM.) for a period of 6 to 8
months. Then the patients were taken off the prescription antihistamines
and instead given a two dosage units twice a day (as described in Example
1 below) of the inventive compound for a period of 6-9 months.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows a graph which indicates that the IgE level (which is a
standard measure of the presence of allergen) in patients taking the
inventive compound was significantly reduced (by 3563) after a patient is
given Applicant's inventive compound when compared with patients the
traditional antihistamine where the reduction was 1275. This demonstrates
that the inventive compound is almost three times as effective in reducing
allergies as currently prescribed commercial brands.
This invention also relates to pharmaceutical dosage unit forms for
systemic administration (oral) which are useful in treating mammals,
including humans to relieve the symptoms of a type I allergic reaction.
The term "dosage unit form" as used in this specification and in the
claims refers to physically discrete units suitable as unitary dosage for
mammalian subjects, each unit containing a predetermined quantity of the
essential active ingredient; calculated to produce the desired effect in
combination with the required pharmaceutical means which adapt said
ingredient for systemic administration. Examples of dosage unit forms in
accordance with this invention are tablets, capsules, orally administered
liquid preparations in liquid vehicles and dry preparations for the
extemporaneous preparation of preparations in a liquid vehicle. Solid
diluents or carriers for the solid oral pharmaceutical dosage unit forms
are selected from the group consisting of lipids, carbohydrates, proteins
and mineral solids, for example, starch, sucrose, kaolin, dicalcium
phosphate, gelatin, acacia, corn syrup, corn starch, talc and the like.
Capsules, both hard and soft, are formulated with conventional diluents
and excipients, for example, edible oils, talc, calcium carbonate, calcium
stearate, magnesium stearate and the like. Liquid pharmaceutical
preparations for oral administration may be prepared in water or aqueous
solutions which advantageously contain suspending agents, such as for
example, sodium carboxymethylcellulose, methylcellulose, acacia, polyvinyl
pyrrolidone, polyvinyl alcohol and the like. Such preparations must be
stable under the conditions of manufacture and storage, and ordinarily
contain in addition to the basic solvent or suspending liquid,
preservatives in the nature of bactericidal and fungicidal agents, for
example, parabens, chlorobutanol, benzyl alcohol, phenol, thimerosal, and
the like. In many cases it is preferable to include isotonic agents, for
example, sugars or sodium chloride. Carriers and vehicles include
vegetable oils, water, ethanol, and polyols, for example, glycerol,
propylene glycol, liquid polyethylene glycol, and the like.
The pharmaceutical dosage unit forms are prepared in accordance with the
preceding general description to provide an effective amount of the
essential active ingredient per dosage unit form in admixture with the
means for adaptation to systemic administration. In general, the unit dose
form will contain 5 to 95 percent by weight of the essential active
ingredient.
It is also contemplated that the composition may be applied topically to
relieve allergic reactions which manifest itself in the form an itch.
Suitable vehicles to act as a pharmaceutically acceptable carriers for
topical administration are found in U.S. Pat. Nos. 5,916,905 and 5,902,827
incorporated herein by reference and are known to those skilled in the
art.
It will be appreciated that the exact dosage of the essential active
ingredient constituting an effective amount for treatment of a mammal
according to the method of the invention will vary greatly depending on
the specific nature of the clinical condition being treated, severity of
the condition, species of mammal; age, weight and condition of the mammal
and the specific formulation being administered. The exact dose required
for a given situation may be determined by administration of a trial dose
and observation of the clinical response. In general, an effective amount
to be administered will be within a range of from about 0.1 mg. per kg. to
about 50 mg. per kg. of body weight of the recipient, daily. Preferably
0.5 mg./kg. to about 25 mg./kg. daily is provided. In most instances. In
cases such as the treatment of hay fever, it may be desirable to repeat
the administrations several times daily over periods of time.
The following examples and preparations describe the manner and process of
making and using the invention and set forth the best mode contemplated by
the inventor of carrying out the invention but are not to be construed as
limiting.
EXAMPLE 1
A mixture of the following ingredients is prepared by hand mixing:
English Name Chinese Name Source Amount
Ginseng 20% ren shen root 100 mg
Ginkgo biloba 24% bai gao leaves 30 mg
Ziziphus suan zao ren seed 20 mg
Mume Fruit wu mei fruit 100 mg
Licorice Root gan cao root 50 mg
The mixture which constitutes the essential active ingredient of the
composition of the invention, may be compounded into wafers, tablets or
capsules containing 330 to 500 mg of active ingredient. In an uncompounded
form, the mixture may be orally administered to an adult human 1 to 4
times a day or as recommended by a health care professional.
Alternatively, the mixture may be mixed with juice, water or food to
facilitate oral administration.
EXAMPLE 2
Three thousand tablets for oral use, each containing 330 to 500 mg of
essential active ingredient are prepared from the following ingredients:
essential active ingredient (Example 1) 1500 g
starch (Rx-1500) 300 g
magnesium stearate, USP 39 g
colloidal silicic acid 19.5 g
Avicel .RTM. pH 102. q.s. to 3900 g
The essential active ingredient is ground through a 0.25 mm sieve opening
screen. The powdered active ingredient, with 50% of the total amount of
magnesium stearate be used, colloidal silicic acid and Ayicel.RTM. pH 10.2
are passed through a 40 mesh sieve, mixed for 20 minutes and then slugged.
The slugs are broken down by forcing through a screen No. 11, and mixed
with the remaining magnesium stearate and compressed into tablets.
One tablet given orally 1 to 4 times a day is useful in the relief of
symptoms of inflammation in adult humans provoked by allergic response, or
like etiological causes.
EXAMPLE 3
Three thousand capsules for oral use, each containing 330 to 500 mg of the
essential active ingredient, from Example 1, supra., are prepared from the
following ingredients:
essential active ingredient (Example 1) 330-500 g
colloidal silicic acid 30 g
magnesium stearate USP 30 g
microcrystalline cellulose 150 g
lactose 90 g
In accordance with the active ingredient potency, the amount of lactose is
adjusted to achieve a weight of 900 mg for each capsule. The ingredients
are passed through a 40 mesh sieve and mixed for 30 minutes. Hard gelatin
capsules No. 0 are filled using Zanazi, model RV-59 equipment. The
capsules are preserved in airtight, light-resistant containers. For
adults, a suggested use: Take 1 to 2 capsules, two times daily during the
allergy season, as a dietary supplement or as directed by a health case
practitioner.
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